First Drug Approved for Niemann-Pick Disease Type C

The FDA on Friday approved arimoclomol (Miplyffa) as the first treatment specifically for the genetic disorder Niemann-Pick disease type C (NPC), an ultra-rare and progressive neurodegenerative disease.

Arimoclomol oral capsules are indicated for the treatment of neurological manifestations of NPC in adults and children ages 2 years and older in combination with miglustat, an enzyme inhibitor.

The approval was based on limited data from a small phase II/III trial in which arimoclomol was associated with slower disease progression on the rescored 4-domain NPC Clinical Severity Scale (R4DNPCCSS), with the primary endpoint comprising ambulation, fine motor skills, speech, and swallowing domains. Study participants had a molecularly confirmed diagnosis of NPC and 78% were on background miglustat treatment.

Through a year of treatment, arimoclomol in combination with miglustat stopped disease progression as measured by R4DNPCCSS, with a 0.2-point decrease from baseline compared with a 1.9-point increase with miglustat alone, drugmaker Zevra Therapeutics noted in its release announcing the approval.

Notably, arimoclomol had been rejected by the FDA in 2021, but gained the support of an advisory committee this past August, with panelists voting in favor of approval based on the large unmet need in NPC and despite the “slightly positive” and “weak” strength of evidence. It is estimated that 900 people in the U.S. are living with the rare disease.

NPC is caused by mutations in the NPC1 or NPC2 genes. It is characterized by a person’s inability to transport lipids inside of cells. The abnormal accumulation of lipids damages organs and is often fatal.

“NPC is a serious disease that leads to enormous adverse impacts on patients and families. Despite extensive research efforts, there have not been approved treatments to meet the significant needs of patients,” Janet Maynard, MD, MHS, director of FDA’s Office of Rare Diseases, Pediatrics, Urologic, and Reproductive Medicine, said in a statement. “The first-ever approval of a safe and effective drug option for NPC will undoubtedly support the essential medical needs of those suffering.”

Arimoclomol’s mechanism of action is unknown.

The drug’s label lists no contraindications but warns of hypersensitivity reactions, potential fetal harm, and substantial increases in serum creatinine of 10-20%. The most common adverse events in trials have been upper respiratory tract infection, diarrhea, and weight loss, with rates of 15% or above.

Arimoclomol is administered orally three times a day, with or without food, with the dosage (47 mg to 124 mg) depending on a patient’s body weight.

Zevra said it expects the drug to be available within 8 to 12 weeks.